1. Field of the Invention
This invention relates to the process of preparation of low molecular weight poly(hydroxyalkanoate)s (PHA) from high molecular weight PHAs by thermal degradation method in a controllable manner. Typical examples are such as thermal degradation of poly((R)-3-hydroxybutyrate) (PHB), poly((R)-3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB/V). This process is suitable for scaling up to industrial production of specified molecular weight polymers of polyester type polymers from their higher molecular weight polymers. It is a typical example of thermal degradation of a bacterial high molecular weight PHA to a desired low molecular weight PHA. In the process, a second component with a high boiling point is used as a ‘solvent’ or ‘additive’ or ‘diluter’. So that the system has better heat transfer, stirring and easier work up after the reaction finishes. The process will produce low molecular weight PHAs for the application such as nano and microspheres used in different areas, such as drug delivery systems, drug coating systems. The low molecular weight PHAs produced in this invention process usually possess functional groups of carboxylic acid end, which can be used for the application of making copolymers of PHA with other components for many different applications such as biodegradable and biocompatible adhesives, drug delivery systems, drug coating systems, and the copolymers could be useful as tissue engineering materials and blending materials for biodegradable materials.
2. Description of Prior Art
PHA (polyhydroxyalkanoate) is a general nomenclature for a class of biopolymers and copolymers originally produced by bacterials. PHA is semicrystalline thermoplastics, ranging from around 70% crystallinity to very low crystallinity. They have the following generic structure:
R can be hydrogen or hydrocarbon chains of up to around C13 in length, and x can range from 1 to 3 or more.
When R is a methyl group and x=1, the polymer is poly(3-hydroxybutyric acid) or poly(3-hydroxybutyrate) (PHB), the basic homopolymer in the PHA family. When R is a ethyl group and x=0.1, the polymer is poly(3-hydroxyvalerate) PHV. Copolymers of PHB/V with different compositions are often produced to control to the melting points and other properties. The polymers of PHA with R≧1 and x=1, produced by bacteria in nature and in industrial controlled fermentation, have a chiral centre. These PHAs are optically active. These polymers are poly((R)-3-hydroxyalkanoate)s, and their structures are illustrated as follows.

Where R1 and R2 can be CH3 or CH3 and CH2CH3 respectively or other substitutes, etc. If R1=R2=CH3, the polymer is Poly((R)-3-hydroxybutyrate), or PHB. If R1=CH3 and R2=CH2CH3, the random copolymer is Poly((R)-3-hydroxybutyrate/valerate), or PHB/V.
PHB and PHB/V are the most common polymers of PHA.
PHAs are biocompatible and biodegradable polymers. Progress in understanding the structure-property relation of bacterially produced poly((R)-3-hydroxyalkanoate)s and their copolymers PHB/Vs is summarized in recent reviews (Marchessault, R. H.; Yu, G.-E., Chapter 17 Crystallization and Material Properties of PHAs, in Handbook of Biopolymers, vol. 5, edited by A. Steinbuchel and Y. Doi, Wiley/VCH Publishers, 2001).
PHB and its copolymers, e.g., PHB/V, can be degraded by purified bacterial enzymes. PHB and its copolymers can also be hydrolysed in acidic and basic conditions, just like normal esters. The study of the hydrolysis of PHB was pioneered by Lemoigne who used the result as a proof of the chemical structure of the PHB chain. Further studies of hydrolysis of PHB in base conditions and precipitation fractionation of the hydrolytic products were carried out by Hauttecoeur et al. Acidic hydrolysis of PHAs under 150° C. to generate functionalised low molecular weight PHAs as reaction blocks has also been useful (U.S. Pat. Nos. 5,268,422 and 5,191,016). The hydrolysis of PHB in basic and acidic conditions has been reviewed in recent paper (Yu, G.-E. et al ‘Characterisation of low molecular weight poly(3-hydroxybutylate)’, Polymer, 2000, 41, 1087-1098).
High molecular weight PHAs can undergo transesterification reactions with diol to generate low molecular weight PHA diols as basic building materials of polyurethane polymers for biodegradable/medical applications (U.S. Pat. No. 5,665,831).
It is well known that PHB and its copolymers PHB/V etc can be thermally degraded. The mechanisms of thermal degradation of PHB and its copolymers are sensitive to the investigated temperature range. At moderate temperatures, it was widely accepted that the PHB was decomposed through a random scission process involving a six-membered ring ester intermediate as illustrated below.

This mechanism has been well accepted to give almost exclusively an unsaturated end and a carboxylic end for another end of the products, as illustrated in scheme 3

The definitions for R1 and R2 are the same as in Scheme 1.
Almost all the publications on the thermal degradation of PHA are concerned with the degradation mechanisms except one from Hoecker's group who decomposed PHB to cyclics and tried to recycle the decomposed products.
When low molecular weight samples of PHB are generated purposely by controlled thermal degradation procedure, a potential synthetic block material is produced due to there are functional ends with the obtained polymers. This has been well described in the invention (U.S. Pat. No. 6,534,599) and literature (Sophie Nguyen, Ga-er Yu, R. H. Marchessault, Thermal Degradation of Poly(3-hydroxyalkanoates): Preparation of Well-Defined Oligomers, Biomacromolecules, 2002, 3(1), 219).
A possible scaling-up process for controlled thermal degradation of PHA to produce desired molecular weight PHA is needed.